Our studies on the ventromedial-dorsomedial hypothalamic (V-DMH) lesioned weanling rat have provided insight into the regulatory influence the central nervous system has on islet cell and gastrointestinal function. The similarities between hypothalamic lesioned rat islet cell function and the altered islet cell function found in many adult type human diabetes are of considerable interest and may indicate a hypothalamic defect (as yet undefined) in some types of diabetes. We propose to investigate the abnormal islet cell function of (V-DMH) lesioned rats by: 1) determining the influence of hypoinsulinemic hypoglycemia (phloridzin induced) on A, -B and D-cell function. 2) investigate further the influence of gastrointestinal hormones such as cholecystokinin octapeptide and gastrin on islet cell function; specifically during nutrient absorption 3) study the influence of gastrointestinal hormones including somatostatin upon the abnormal rate of absorption of fluroescein. 4) investigate in normal and lesioned rats the influence of neurotransmitters such as (GABA) and taurine upon islet cell function and gastrointestinal absorption of fluroscein. 5) study the effect of a 3 day fast upon A and B-cell response to intragastric and intravenous glucose. 6) continue our studies on the abnormal pancreatic islet and exocrine cell morphology in both (V-DMH) lesioned rats and 129J mice by applying the protein A-Gold technique. 7) tissue (stomach and pancreas) concentrations of somatostatin insulin and glucagon will be determined during fasting and phloridzin induced hypoglycemia. The major significance of the work will be a greater understanding of the hypothalamus regulation of islet cell function; specifically those factors which influence the glucose sensing ability of pancreatic A-cells.